We propose to supplement the Alzheimer's Disease Neuroimaging Initiative (ADNI) study by imaging amyloid plaque burden with positron emission tomography (PET) and Pittsburgh Compound B (PIB) in a subset of ADNI subjects who are scheduled to receive [F-i8]2-fluoro-2-deoxyglucose (FDG) PET scans as part of the funded five year ADNI imaging protocol. Neuropathologically, Alzheimer's disease (AD) is defined by the presence of plaques composed of the amyloid-beta (Ap) protein. This alone makes identification of AD pathology in living subjects an important goal because it could allow refinement of early diagnosis and identification of pre-symptomatic pathology for use as a biomarker. In addition, the optimal development of new anti-amyloid therapies will require a means to monitor brain amyloid load. PIB PET scans will be conducted in 24 control, 48 mild cognitive impairment (MCI), and 24 AD subjects at 16 ADNI PET sites immediately prior to FDG PET scans in subjects enrolled in the ADNI FDG PET imaging protocol. Controls and MCI subjects will be scanned at entry (baseline), 12, 24, and 36 months. AD subjects will be scanned at baseline, 12 and 24 months. These supplementary PIB PET studies will make full use of ADNI resources including administrative support of the ADNI Coordinating Center at UC San Diego as well as of existing MR and PET scanner quality control programs and data storage, management, and retrieval programs. Investigators at the University of Pittsburgh will analyze the PIB PET data using established image-based methods and post the results on the ADNI Laboratory of Neuroimaging (LONI) server for dissemination. The proposed supplemental PIB PET studies will provide unique, yet complementary, functional imaging data of the prevalence and amount of AP plaque binding in these subjects and further extend the objectives, hypotheses, and specific aims of the original ADNI grant. Specific Aims of the PIB PET Supplement include: i) determine differences in the quantity and regional distribution of PIB retention in control, MCI, and AD subjects and relate these differences to cognitive, glucose metabolic, and structural MR measures in the same subjects collected by ADNI investigators; 2) determine how the quantity and regional distribution of PIB retention changes over time in control, MCI, and AD subjects and relate these changes to cognitive, glucose metabolic, and structural MR change measures determined in the same subjects by ADNI investigators; and 3) correlate PIB retention in whole brain and individual regionsof-interest to blood, urine and CSF biomarkers. [unreadable] [unreadable] [unreadable]